Titles and Affiliations
Professor of Oncology
Sidney Kimmel Comprehensive Cancer Center
Research area
Revealing the molecular links between obesity, the microbiome, and breast cancer and developing strategies to disrupt them.
Impact
Obesity is correlated with increased breast cancer risk in post-menopausal women. The prevalence of obesity in the United States and increasing rates observed worldwide make it a global health crisis. Dr. Sharma and her team study the molecular changes induced by obesity that promote breast cancer development, progression, and metastasis. They also focus on the intersections between obesity and the microbiome (the bacteria that reside throughout our body). Many studies found that the complex makeup of the microbiome changes with disease or other alterations to our physiology— including obesity—and these changes in bacterial populations may have profound effects on the body. Dr. Sharma’s team is working to reveal how obesity, and obesity-induced changes in the microbiome, may influence breast cancer.
Progress Thus Far
Dr. Sharma and her team have identified several naturally occurring compounds and showed that they can inhibit breast tumor growth and metastasis in laboratory models with obesity-related hormonal changes. The team also found that fat cells residing within breast tissue play an important role in helping tumors progress and tested several strategies to counter this effect. The team has also identified harmful gut bacteria that promote cancer development and progression and beneficial gut bacteria that may help protect against it. They are now working to develop a bacteria-based approach to shift the gut microbiome toward a healthier state. Early data suggest this bacteria-based approach can inhibit breast cancer cells, alter the tumor microenvironment, and improve how well tumors respond to immunotherapy.
What’s next
Dr. Sharma’s team will study how their bacteria-based intervention affects breast cancer cells and the surrounding tumor microenvironment, and how it changes the gut microbiome and circulating metabolites in patients with breast cancer. They will evaluate how well it improves the effectiveness of combined chemotherapy and immunotherapy in laboratory models. They also plan to develop a more advanced formulation that combines beneficial bacteria with compounds designed to reshape the gut environment. This intervention aims to shift gut bacteria toward producing molecules that support anti-tumor immunity, reverse metabolic changes that suppress the immune system, and support weight loss to help counter obesity-driven cancer growth. Success in these studies will provide the evidence needed to move these approaches toward clinical trials, offering new hope for prevention and treatment in a patient group with urgent needs.
Biography
Dipali Sharma, PhD is a Professor in the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. She obtained her doctorate in Molecular Biology and Oncology from the University of Delhi. She then completed fellowships at both the University of Maryland and the Sidney Kimmel Comprehensive Cancer Center.
The prevalence of obesity, an epidemic of major proportions in the United States today, has risen steadily over the last several decades. Research on the biological mechanisms underpinning the link between cancer and obesity is clearly a vitally important area, with major implications for both public health and fundamental cancer research. Dr. Sharma focuses on investigating the molecular links between obesity and cancer, emphasizing aspects that have potential clinical significance. Her studies on obesity-related hormones, adipocytokines, showed that leptin promotes the proliferative response and metastatic potential as well as modulates the expression of various genes involved in cell cycle, apoptosis and metastasis. Her lab is exploring the genes, molecules, hormones and cellular processes that could cause and promote cancer in obese people. Using various physiologically relevant models and cell lines, their aim is to find molecular targets that can be disrupted to break the obesity-cancer axis. She is exploring new strategies to disrupt the obesity-cancer connection using novel small molecule inhibitors as well as bioactive food components. Her overall goal is to understand the molecular networks by which obesity affects carcinogenesis and discover novel agents to effectively disrupt obesity-cancer axis.
